Project Summary Hip fractures remain one of the most devastating and costly clinical problem affecting older adults. Each year over 300,000 older people sustain hip fracture in the U.S., up to 25% of hip fracture patients die within a year of their injury, and hip fractures account for ~72% of the overall $17 billion cost for osteoporotic fractures. The current clinical standard for assessment of fracture risk is bone mineral density (BMD) testing by dual-energy x-ray absorptiometry (DXA) combined with clinical risk factors. However, half of all fractures occur in those who do not have osteoporosis by BMD testing and/or who have few clinical risk factors, and thus do not meet the WHO fracture risk assessment tool (FRAX) intervention thresholds. Despite the fact that >90% all hip fractures are due to a fall, the current approaches of hip fracture risk do not directly include the probability of falling or the skeletal loading that likely occurs during fall. Our overall goal is to improve the prediction of hip fracture risk by using a biomechanical framework that accounts for the risk of falling, the impact loading due to a fall and femoral strength. In a prospective case-cohort study of 3500 older adults from the AGES Reykjavik study we will develop a subject-specific fall risk tool to evaluate the probability of falling from baseline data including age, sex, fall history, neuromuscular function, dynamic balance, vision and medication use to predict fall occurrence at follow-up (Aim 1). Furthermore, in a prospective case-cohort study of 698 cases and 2792 controls from the AGES-Reykjavik cohort we will test whether a biomechanical approach that compares subject-specific forces applied to the hip during a sideways fall to femoral strength and accounts for subject-specific probability of falling improves hip fracture prediction beyond the current clinical standard (Aim 2). This project will have high impact, as the results will lead to better understanding of the contribution of fall risk, impact loading and femoral strength to hip fracture, that is needed to enable the design of interventions that might be effective in fall prevention and thus, reduce the burden of hip fractures.